Human low density lipoprotein (LDL) exists in either a monodisperse or polydisperse state. Polydisperse LDL is most commonly found in association with hypertriglyceridemia and diabetes mellitus. Physical studies on polydisperse LDL reveal a family of discrete lipoproteins within the LDL class which differ in molecular size. Metabolic studies now completed indicate that in these patients there is a striking increase in the rate of synthesis of VLDL, and that approximately half of the newly synthesized VLDL is removed directly from plasma without being converted to LDL. The remaning VLDL undergoes a metabolc conversion to LDL and then is degraded sequentially, forming initally Sf 20, then Sf 10 and finally Sf 4 LDL, which is removed from plasma. The objectives of this study during the forthcoming year are primarily to focus on the biological role of these various polydisperse low density lipoproteins. A variety of experimental approaches are being explored, such as the use of tissue culture and an attempt to isolate a membrane fragment containing the LDL receptor binding activity, which can be used to study the interaction of the receptor with the various LDL macro-molecules. We are also initiating a study of the physical chemistry of apoB recovered from polydisperse LDL in order to compare this apoB isolated from the normal LDL. Finally, we are undertaking a physical and chemical characterization of HDL2 and HDL3.